Series Of Α-aminophosphonates Research Articles

Efficient synthesis, crystallography study, antibacterial/antifungal activities, DFT/ADMET studies and molecular docking of novel α-aminophosphonates

An efficient method for the synthesis of a new series of α-aminophosphonates has been developed in a one-pot Kabachnik-Fields reaction of 4-methylaminophenol with various aldehydes and triethylphosphite under microwave irradiation and neat conditions using ZnO nanoparticles as a reusable and heterogeneous catalyst, with 82–93% yield at 250 Hz within 2-5 min. A single crystal of the studied compound 3e was selected for X-ray diffraction analysis, it crystallizes in the monoclinic crystal system with P 21/n space group. All the compounds were evaluated for their antimicrobial against a panel of Gram-negative pathogenic bacteria such as Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Serratia marcescens, Morganella morganii, Pseudomonas aeruginosa and Gram-positive :Staphylococcus aureus and against fungi : Candida albicans, Candida krusei, Candida kefyr, Candida lusitaniae, and Candida tropicalis. Further in silico target hunting reveals the antibacterial activity of the designed compounds by inhibiting Dihydropteroate synthase and all the designed compounds have shown significant drug-like characteristics.

Microwave-assisted synthesis of novel sulfonamide-based compounds bearing α-aminophosphonate and their antimicrobial properties

A series of α-aminophosphonates (3a-3m) bearing the sulfisoxazole moiety was synthesized through one-pot Kabachnik-Fields reaction of sulfisoxazole, diethyl phosphite (DEP) and substituted aldehydes using bismuth (III) triflate [Bi(OTf)3] as a catalyst under microwave reaction conditions. The novel compounds are identified by their spectroscopic data and confirmed by X-ray diffraction studies of diethyl (4-chlorophenyl)(4-(N-(3,4-dimethylisoxazol-5-yl)sulfamoyl)phenylamino) methylphosphonate 3g. The antimicrobial properties of the synthesised agents were examined against a range of bacterial species and C. albicans yeast. Some of the synthesised agents, 3j, 3l and 3m, exhibit potent antimicrobial activities against the five pathogenic microorganisms used in the investigation. Compound 3m is the most promising agents among all the synthesized derivatives, showing a potent and broad-spectrum antibacterial activity. The MIC values are 94.2 and 205.7 µM for 3m and sulfisoxazole, respectively for S. typhi (about 2.1 times potency). The MIC values are 102.8 and 187.0 µM for 3m and sulfisoxazole, respectively for L. monocytogenes. The observed biological properties are explained and supported by QSAR models.

Synthesis of novel α-aminophosphonates under microwave irradiation, biological evaluation as antiproliferative agents and apoptosis inducers

The synthesis of two series of α-aminophosphonates was achieved by Microwave Irradiation (MW), using the one-pot Kabachnik–Fields reaction. Based on a green chemistry approach, the reactions were carried out using ethanol as the only solvent and without any catalyst, and short reaction times (20–40 min), in variable yields. Both series were tested to determine their cell proliferation inhibition activity in MDA-MB-231, MCF-7 and MCF-10A cell lines. Ethyl 4-(((diphenoxyphosphoryl)(4-(diphenylamino)phenyl)methyl)amino) benzoate 4e and diphenyl (((4-(((S)-2-hydroxy-1-phenylethyl)carbamoyl)phenyl)amino)(4-hydroxyphenyl)methyl)phosphonate 6b, showed cell proliferation inhibition activity only in the cancer cell line MCF-7 and no effect on the normal cell line MFC-10A, both compounds caused cell death by inducing apoptosis.

One-pot green synthesis and cytotoxicity of new α-aminophosphonates

A novel series of α-aminophosphonates containing the trifluoromethyl aniline moiety were obtained in high yields by condensation of 2-methyl-3-trifluoromethyl aniline, aryl/heteroaryl aldehydes and dimethylphosphite in the presence of chitosan as a catalyst. The molecular modeling studies revealed their important structural features of binding affinities towards the target enzyme. The cytotoxicity of these compounds was evaluated against PC-3(prostate cancer), MCF-7 (breast cancer), HeLa(cCervix Cancer), U973, K562 and HL60 human lLeukemia cell lines. Compound 4k with a pyrene moiety showed high potency against a breast cancer cell line, while compounds 4g and 4k exhibited more promising cytotoxicity against U973, K562 and HL60 cell lines.

A heterogeneous catalyst, SiO2-ZnBr2: An efficient neat access for α-aminophosphonates and antimicrobial activity evaluation

An efficient, environmentally benign and green method was developed for the synthesis of α-aminophosphonates by one-pot three-component reaction (Kabachnik-Fields reaction) of amine (4-(4-chlorophenoxy)aniline), aldehydes and diethyl phosphite using catalyst, SiO2-ZnBr 2 under solvent-free conditions. The developed method under conventional conditions was further optimized in microwave and ultrasonication methods. A series of α-aminophosphonates, diethyl (4-(4-chlorophenoxy)phenylamino)(aryl/ heteroaryl)methylphosphonates was synthesized to check the generality. The catalyst, SiO2-ZnBr2 afforded good yields of products in all the methods in the range of 85–97% but variation was observed in reaction time. Microwave irradiation method took very less time (4–8 min) as compared with ultrasonication (35–52 min) and conventional (2–3 h) conditions. The major advantages are simple and mild conditions, short reaction times, high yield of the product with purity, use of cheap catalyst and reusability of the catalyst until to three times without significant loss of activity. Antibacterial and antifungal activities were evaluated for the title compounds (50 and 100 μg/mL) including minimum inhibitory concentrations. A few of the newly synthesized α-aminophosphonates exhibited promising antimicrobial activity at lower MIC values in the range of 15.0–25.0 μg/mL and closer to the standards (5–12 μg/mL). An efficient, neat and green method was developed for α-aminophosphonates by Kabachnik-Fields reaction using catalyst, SiO2-ZnBr2. The developed method under conventional conditions was further optimized in microwave and ultrasonication methods. SiO2-ZnBr2 catalyst afforded good yields of the products (85-97%). Molecules were evaluated for antimicrobial activity including their MIC.

ChemInform Abstract: An Eco‐Friendly Three Component Manifold for the Synthesis of α‐Aminophosphonates under Catalyst and Solvent‐Free Conditions, X‐Ray Characterization and Their Evaluation as Anticancer Agents.

A series of α-aminophosphonates were synthesized through one-pot condensation of aryl aldehydes, aryl amines and diethyl phosphite in the absence of any catalyst and organic solvents. All the synthesized α-aminophosphonates were characterized by spectral and elemental analysis and in the case of compound 4j by X-ray crystallography. Some of these new α-aminophosphonate derivatives were found to have cytotoxic activity on the cancer cell line DU145 in vitro by the MTT method.

Design, Synthesis, and Antiviral Activity of α-Aminophosphonates Bearing a Benzothiophene Moiety

A series of α-aminophosphonates containing a benzothiophene moiety was designed and synthesized. All synthesized compounds were confirmed by 1H NMR, 13C NMR, 31P NMR, infrared spectroscopy, and elemental analysis. The half-leaf method was used to determine the in vivo efficacy of α-aminophosphonates bearing a benzothiophene moiety against the tobacco mosaic virus (TMV). Bioassay results showed that all compounds exhibited certain anti-TMV activity at 500 μg/mL concentration. Compound 2f exhibited a curative effect of up to 48.1% against TMV, which was almost similar to that obtained from the standard ningnanmycin (51.9%). [Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]

The Synthesis and Bioactivity of Dimethyl (2,3- Dihydrobenzo[b][1,4]Dioxin-6-Yl)(Aryl Amino)Methylphosphonates

A new series of α-aminophosphonates have been synthesized by a one-pot three-component reaction of 2,3-dihydrobenzo[b][1,4]dioxine-6-carbaldehyde, various amines, and dimethyl phosphite by using nano-TiO2 as a catalyst under solvent-free conditions at 50°C. The major advantages of the present method are high yields, short reaction times, recyclable catalyst, and solvent-free reaction conditions. Among these new structurally diversified set of α-aminophosphonates, dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(3-nitrophenylamino) methylphosphonate and dimethyl (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(4-fluoro-3-nitro-phenyl-amino) methylphosphonate have shown higher antioxidant activity in diphenyl picryl hydrazyl (DPPH) scavenging, reducing power assay, and lipid peroxidation methods.

Design, Synthesis, and Antiviral Activity of α-Aminophosphonates Bearing a Benzothiophene Moiety

Abstract A series of α-aminophosphonates containing a benzothiophene moiety was designed and synthesized. All synthesized compounds were confirmed by 1H NMR, 13C NMR, 31P NMR, infrared spectroscopy, and elemental analysis. The half-leaf method was used to determine the in vivo efficacy of α-aminophosphonates bearing a benzothiophene moiety against the tobacco mosaic virus (TMV). Bioassay results showed that all compounds exhibited certain anti-TMV activity at 500 μg/mL concentration. Compound 2f exhibited a curative effect of up to 48.1% against TMV, which was almost similar to that obtained from the standard ningnanmycin (51.9%). [Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfer, and Silicon and the Related Elements for the following free supplemental files: Additional text, figures, and tables.]

Synthesis and antimicrobial activity of α-aminophosphonates containing chitosan moiety

A novel series of α-aminophosphonates containing chitosan moiety was obtained in high yields from reactions of chitosan with aromatic aldehydes and triphenylphosphite in the presence of lithium perchlorate as a catalyst. The structures of the synthesized compounds were confirmed by IR and 1H NMR spectral data. Compounds (1–4) showed high antimicrobial activities against Escherichia coli (NCIM2065), Serratia marcescens, Enterobacter cloacae, Shigella dysenteriae, Salmonella enterica and Proteus vulgaris as Gram-negative bacteria, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292) as Gram-positive bacteria and Candida albicans as a fungus, at low concentrations (2.5–10mg/mL).

Partition constants of α-aminophosphonates in two-phase aqueous-organic solvent systems

Two-phase potentiometric titration was used to determine partition constants for a series of α-aminophosphonates (RO)2P(O)CH2NR1R2 [R = Alk (C2-C5), R1, R2 = Me, Et, (CH2)5] between water and organic solvents, such as chloroform, carbon tetrachloride, toluene, octane, n-octanol, nitrobenzene, o-xylene, and cyclohexane. Correlations between the partition constants and the number of carbon atoms in substrate molecules were obtained. Solvent effects on partition constants were discussed, and solution parameters of α-aminophosphonates were calculated.